This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The overall hypothesis to be tested by the proposed simulations is that there are measurable differences in the dynamics of intrinsically disordered proteins as compared to denatured forms of natively folded proteins. As part of a project to study FG-nucleoporins (intrinsically disordered proteins that facilitate transport in the nuclear pore complex) we have developed new computational tools to characterize the structural properties of diverse ensembles of protein conformations. One approach, based on metric scaling, allows the calculation of the effective dimensionality of the protein dynamics from the MD trajectory. We have applied this method to relatively short, implicit solvent simulations of intrinsically disordered proteins and denatured forms of natively folded proteins. This yielded intriguing preliminary results indicating that intrinsically disordered proteins might have distinct dynamics from denatured proteins at timescales much shorter than protein folding. However, much longer, microsecond-scale, explicit solvent simulations are necessary to validate these results. If successful, this study will provide new insights to the nature of protein folding, the denatured state, and intrinsically disordered proteins, as well as validate a new tool for characterizing long timescale protein simulations. The proposal requests 49,000 Anton CPU-hours to perform conventional NPT MD simulations on eight different protein systems of ~80,000 atoms for a total simulation time of 28 microseconds.